No Age Limit for Bone Marrow Transplantation

Age is no longer a consideration when determining whether an older patient with blood cancer is a candidate for stem cell transplantation. That was the conclusion two years ago of the first study summarizing long-term outcomes from a series of prospective clinical trials of patients age 60 or older treated with nonmyeloablative transplants, known as mini-transplants, developed at Fred Hutchinson Cancer Research Center. The findings were published November 2, 2011, in the Journal of the American Medical Association.1

On April 20, 2013, the Journal of Clinical Oncology published results with more definitive data from nearly 1100 patients that showed comorbidities contribute significantly to poorer transplant outcomes.2 The study involved patients who were enrolled in prospective multicenter clinical trials between 1997 and 2009. All were age 60 or older; all were treated with the same nonmyeloablative regimen, developed at Fred Hutch; and all had acute or chronic leukemia, lymphoma, multiple myeloma, myelodysplastic syndromes (which can progress to acute myeloid leukemia if not treated), or myeloproliferative diseases, such as chronic myelogenous leukemia.

Both comorbidities and a higher degree of cancer aggressiveness affected survival among these older patients. For example, patients who had fewer comorbidities and less aggressive cancer had a fiveyear survival rate of 60%, while patients with more comorbidities and more aggressive cancer had a survival rate of 30%, regardless of age.

Although survival rates of 30% to 60% may seem low, these patients all would have died of their diseases within a matter of months without a transplant. The majority of patients were referred for a transplant after they had exhausted all forms of conventional therapy.

Conventional Versus Nonmyeloablative Transplants

While there is much room for improvement, particularly with regard to relapse, these results are encouraging given the poor outcomes with nontransplant treatments, especially for patients with high-risk acute myeloid leukemia, fludarabine-refractory chronic lymphocytic leukemia, or progressive lymphoma.

Nonmyeloablative transplantation was developed by researchers at Fred Hutch specifically for older and sicker patients who could not tolerate the more toxic, highdose regimens used to prepare patients for conventional transplantation.

Conventional transplants, which are generally not performed for people who are over age 60 or are medically unfit, require high doses of total body irradiation and potent chemotherapy to eliminate cancer cells. This intense treatment destroys the patient’s blood and immune system and is fatal unless the patient is rescued by an infusion of bone marrow or stem cells from a donor.

Nonmyeloablative transplants, in contrast, rely on the ability of donor immune cells to target and destroy the patient’s cancer without the need for such high doses of radiation and chemotherapy. Instead, moderate-dose radiation and chemotherapy are used to suppress, but not destroy, the patient’s immune system. This helps the body accept the donor cells, which then go to work attacking the patient’s cancer—called the graft-versus-tumor effect—and rebuilding the patient’s immune system.

Relapse Rates

In addition to survival and the impact of comorbid conditions, the 2013 study examined rates of relapse, hospitalization, acute and chronic graftversus- host disease (GVHD), and the toxicity of the treatment to internal organs. In one key finding, disease-relapse risks, not increasing age, were associated with worse outcomes. Other data showed that two-thirds of the surviving older patients who were affected by chronic GVHD had complete resolution of their symptoms and were able to discontinue immunosuppressive medications after a median time of two-and-a-half years from diagnosis. This was comparable to the results reported by previous studies on younger patients who were treated with high-dose radiation and chemotherapy. Half of the older patients never required hospitalization after transplant.

For additional insight on new agents and other emerging CLL therapies, OncLive spoke with Thomas Kipps, MD, PhD, professor of Medicine in the Division of Hematology-Oncology, and Deputy Director for Research at the UC San Diego Moores Cancer Center.